Experimental autoimmune encephalomyelitis (EAE) is the primary disease model of multiple sclerosis (MS), one of the most diffused neurological diseases characterized by fatigue, muscle weakness, vision loss, anxiety and depression. EAE can be induced through injection of myelin peptides to susceptible mouse or rat strains. In particular, EAE elicited by the autoimmune reaction against myelin oligodendrocyte glycoprotein (MOG) presents the common features of human MS: inflammation, demyelination and axonal loss. Optic neuritis affects visual pathways in both MS and in several EAE models. Neurophysiological evaluation through visual evoked potential (VEP) recording is useful to check visual pathway dysfunctions and to test the efficacy of innovative treatments against optic neuritis. For this purpose, we investigate the extent of VEP abnormalities in the dark agouti (DA) rat immunized with MOG, which develops a relapsing-remitting disease course. Together with the detection of motor signs, we acquired VEPs during both early and late stages of EAE, taking advantage of a non-invasive recording procedure that allows long follow-up studies. The validation of VEP outcomes was determined by comparison with ON histopathology, aimed at revealing inflammation, demyelination and nerve fiber loss. Our results indicate that the first VEP latency delay in MOG-EAE DA rats appeared before motor deficits and were mainly related to an inflammatory state. Subsequent VEP delays, detected during relapsing EAE phases, were associated with a combination of inflammation, demyelination and axonal loss. Moreover, DA rats with atypical EAE clinical course tested at extremely late time points, manifested abnormal VEPs although motor signs were mild. Overall, our data demonstrated that non-invasive VEPs are a powerful tool to detect visual involvement at different stages of EAE, prompting their validation as biomarkers to test novel treatments against MS optic neuritis.

中文翻译：

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非侵入性视觉诱发电位评估由髓鞘少突胶质细胞糖蛋白诱导的实验性自身免疫性脑脊髓炎暗刺鼠模型中的视神经受累。

实验性自身免疫性脑脊髓炎 (EAE) 是多发性硬化症 (MS) 的主要疾病模型，MS 是最广泛的神经系统疾病之一，其特征是疲劳、肌肉无力、视力丧失、焦虑和抑郁。EAE 可以通过将髓鞘肽注射到易感的小鼠或大鼠品系来诱导。特别是，针对髓鞘少突胶质细胞糖蛋白 (MOG) 的自身免疫反应引起的 EAE 具有人类 MS 的共同特征：炎症、脱髓鞘和轴突丢失。视神经炎影响 MS 和几种 EAE 模型中的视觉通路。通过视觉诱发电位 (VEP) 记录进行的神经生理学评估有助于检查视觉通路功能障碍并测试针对视神经炎的创新疗法的疗效。以此目的，我们调查了用 MOG 免疫的暗刺鼠 (DA) 大鼠 VEP 异常的程度，其发展了复发-缓解病程。连同运动体征的检测，我们在 EAE 的早期和晚期都获得了 VEP，利用允许长期随访研究的非侵入性记录程序。VEP 结果的验证是通过与 ON 组织病理学的比较来确定的，旨在揭示炎症、脱髓鞘和神经纤维丢失。我们的结果表明，MOG-EAE DA 大鼠的第一个 VEP 潜伏期延迟出现在运动缺陷之前，主要与炎症状态有关。在复发性 EAE 阶段检测到的后续 VEP 延迟与炎症、脱髓鞘和轴突丢失的组合有关。而且，具有非典型 EAE 临床病程的 DA 大鼠在极晚的时间点进行测试，尽管运动症状轻微，但表现出异常的 VEP。总体而言，我们的数据表明，非侵入性 VEP 是检测 EAE 不同阶段视觉受累的强大工具，促使它们作为生物标志物进行验证，以测试针对 MS 视神经炎的新型治疗方法。